The effect of mycophenolate mofetil and azathioprine dose on renal allograft outcome in the United kingdom.
BACKGROUND
Mycophenolate mofetil (MMF) therapy compared with azathioprine has not led to improved long-term renal allograft outcomes perhaps as MMF dose is limited by tolerability and dose reduction is associated with inferior graft outcome. The consequences, however, of dose reduction of mycophenolate mofetil relative to azathioprine have not been reported.


METHODS
We studied dosing patterns of MMF and azathioprine in the first year after transplantation and their impact on graft outcome after renal transplantation between 1999 and 2002 in the United Kingdom.


RESULTS
Sixty-two percent of patients were found to be taking less than 2 g of MMF and 45% were taking less than 100 mg of azathioprine at 1 year after transplantation. Graft outcome was comparable in patients receiving 2 g or more of MMF (n=209), 1 to 2 g of MMF (n=267), and 100 mg or more of azathioprine (n=504) at 1 year after transplantation. Less than 1 g of MMF (n=71) and less than 100 mg of azathioprine (n=413) was associated with a 3-fold and 2-fold increased 4.5 year risk-adjusted hazard ratio (HR) of graft failure, respectively, with reduced graft function. Finally, less than 1 g of MMF was not superior to less than 100 mg of azathioprine.


CONCLUSIONS
Azathioprine levels are not routinely measured and long-term results of concentration controlled MMF studies are awaited. Currently, dose is a useful measure of drug exposure. This study suggests that less than 1 g of MMF and less than 100 mg of azathioprine are associated with inferior graft outcome.
Shah
Sapna
S
Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom. sapnashah100@hotmail.com
Collett
Dave
D
Johnson
Rachel
R
Raftery
Martin
M
Rudge
Chris
C
Yaqoob
Mohammad M
MM
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D006113:United Kingdom
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine